EP0466092A1 - Vaginal pharmaceutical preparation - Google Patents

Abstract

The vaginal pharmaceutical preparation is characterised in that it contains at least one water-soluble polyvinyl alcohol, at least one component A selected from the group consisting of wetting agents, non-ionic surface-active agents and dispersants, and at least one active substance B for the local treatment of sexually transmissible or transmitted diseases, and/or vaginal disorders, and optionally one or more auxiliary or auxiliaries, in homogeneous dispersion, and is in the form of a film with a thickness of 0.05 to 0.5 mm, in particular 0.06 to 0.2 mm, preferably 0.07 to 0.15 mm.

Description

The vorxegenae fatigue concerns a pnarmazeuuscnes, vaginai preparation to be applied.

Vaginal tablets, ointments, gels, foams and ovules are mainly used for the pharmaceutical treatment of vaginal diseases. Each of these dosage forms has advantages and disadvantages. The disadvantages to be mentioned are: poor disintegration of the preparation, foreign body sensation, poor distribution of the respective active substance on the vaginal mucosa, complicated dosage, for example using an applicator. Foam can cause an uncomfortable feeling and can therefore be rejected for objective and / or subjective reasons. Furthermore, a so-called C-film for the prevention of pregnancy is known.

It is an object of the present invention to provide a new pharmaceutical form, namely a film, for the metered delivery of the active ingredients for the local treatment of sexually transmitted or resp. to transmit transmitted diseases and / or vaginal affections. This new galenic form is supposed to distribute the active substances on the vaginal mucosa relatively quickly, well and evenly. The stability of the active compounds present in the film should also be increased.

These goals are achieved in an excellent manner with the preparation according to the invention.

The pharmaceutical preparation according to the invention to be administered vaginally is characterized in that it contains at least one water-soluble polyvinyl alcohol, at least one component A, selected from the group consisting of wetting agents, nonionic surface-active agents and dispersants, and at least one active ingredient B for the local treatment of sexually transmitted, resp. transmitted diseases, and / or vaginal affections, and optionally one or more auxiliary substance (s), homogeneously distributed, and in the form of a film with a layer thickness of 0.05 to 0.5 mm, in particular 0.06 to 0.2 mm , preferably 0.07 to 0.15 mm, is present.

Preferred embodiments of this invention are defined in the dependent claims.

The possible production of the preparation according to the invention is described below.

worin n eine ganze Zahl, vorzugsweise die Zahl 9 oder 10, bedeutet,und Glycerin, und mit Wasser vermischt. Danach wird diese Mischung erwärmt, beispielsweise auf eine Temperatur von etwa 90 C. Es ist bevorzugt, die abgekühlte Lösung, beispielsweise bei einer Temperatur von etwa 50 C, zu filtrieren. Falls der Wirkstoff B und die gegebenenfalls zu verwendenden Hilfsstoffe in Wasser löslich sind, werden sie in Wasser gelöst, und vorzugsweise vor der Filtration der Mischung zugegeben. Falls der Wirkstoff B und die gegebenenfalls zu verwendenden Hilfsstoffe in Wasser nicht löslich sind, werden sie nach der genannten Filtration der Mischung, vorzugsweise unter Rühren, zugegeben, beispielsweise in der Form einer Suspension oder Emulsion, wobei wässrige Suspensionen oder Emulsionen bevorzugt sind. Wasser- in-Oel-Mikroemulsionen und Oel-in-Wasser-Mikroemulsionen sind ebenfalls anwendbar. Es ist auch möglich, einen in Wasser nicht löslichen Wirkstoff B und/oder Hilfsstoff in fester Form, vorzugsweise unter Rühren, der filtrierten Mischung zuzugeben, insbesondere dann, wenn die Suspension homogenisiert wird. Es ist auch möglich, den Wirkstoff B und/oder Hilfsstoff in wenigstens einem organischen Lösungsmittel gelöst der Mischung zuzugeben. Bei dieser Art der Zugabe darf es zwischen organischem Lösungsmittel und Wasser keine Phasentrennung geben. Wenn nötig kann zum Korrosionsschutz von Filmherstellungsvorrichtungen die Filmgiesslösung gepuffert werden.A water-soluble polyvinyl alcohol, for example Poval 205 from Kuraray Co. Ltd., Japan, is mixed with at least one ingredient A, for example a mixture of at least one nonoxynol, such as nonoxynols of the formula

wherein n is an integer, preferably the number 9 or 10, and glycerol, and mixed with water. This mixture is then heated, for example to a temperature of approximately 90 ° C. It is preferred to filter the cooled solution, for example at a temperature of approximately 50 ° C. If the active ingredient B and the auxiliaries to be used, if appropriate, are soluble in water, they are dissolved in water and are preferably added before the mixture is filtered. If the active ingredient B and the auxiliaries to be used, if appropriate, are not soluble in water, they are added to the mixture after the said filtration, preferably with stirring, for example in the form of a suspension or emulsion, aqueous suspensions or emulsions being preferred. Water-in-oil microemulsions and oil-in-water microemulsions can also be used. It is also possible to add a water-insoluble active ingredient B and / or auxiliary in solid form, preferably with stirring, to the filtered mixture, in particular when the suspension is homogenized. It is also possible to add the active ingredient B and / or auxiliary to the mixture in solution in at least one organic solvent. With this type of addition, there must be no phase separation between organic solvent and water. If necessary, the film casting solution can be buffered to protect film production devices from corrosion.

The filtration mentioned is carried out in order to remove any impurities, such as water-insoluble polyvinyl alcohol polymers, dust and other foreign particles. Filtration could be dispensed with for absolutely clean and uniform products. The film casting solution must be homogeneous. Any air bubbles that may be present can be removed by allowing the solution to stand or by means of a vacuum or by means of gentle stirring.

This film casting solution can now be processed into a film in a conventional manner in several ways.

In a first type, the film casting solution is poured into a tub, which has the desired dimensions. The water and any organic solvents which may be present are then removed by drying. Drying can take place, for example, by means of hot air coming from a suitable hairdryer or a suitable heating lamp, for example an infrared lamp. The temperature used in each case must be such that no component due to heat The film can now be embossed, which increases its surface and grip. The film is then cut and packaged, eg packed in sachets, and can be made sterile if necessary using a suitable radiation method.

In a second type, the film casting solution is continuously processed in a film casting device. The film casting solution is poured through a slot nozzle onto a running belt. This film carrier is usually a high-gloss chrome steel strip. When casting, the viscosity of the film casting solution must be such that it still flows but does not stop.

The viscosity used in each case includes depending on the machine type. The running belt coated with the film casting solution is passed through a drying tunnel, in which the water and the organic solvent which may be present are removed. The temperature used in the drying tunnel must be such that no component is chemically converted, in particular decomposed, by the action of heat. At the end of the drying tunnel, the film contains only a few% by weight of water, for example about 5% by weight of water. The desired film thickness can be monitored and controlled by a computer. If, for example, the advance of a film is too thin, the slot nozzle is automatically opened slightly. If, on the other hand, the film is too thick, the slot nozzle is closed somewhat. With regard to embossing, cutting and assembly, reference is made to the above-mentioned explanations.

worin n eine ganze Zahl, vorzugsweise die Zahl 9 oder 10, bedeutet. Nonoxynol-9 und Nonoxynol-10 sind bevorzugt, insbesondere dann, wenn diese Verbindungen die Vorschriften gemäss USP 22 erfüllen.The active ingredient B for the local treatment of sexually transmitted, resp. transmitted diseases and / or vaginal affections is in particular an active ingredient for the local treatment of bacterial or viral infections or an active ingredient for the local treatment of diseases caused by fungi or trichomonads. Examples include: benzalkonium chloride, neomycins, such as neomycin B sulfate, polymyxins, such as polymyxin B sulfate, econazole, econazole nitrate and metronidazole. These and other active compounds, including a placenta extract, can be mixed with a nonoxynol, for example with nonoxynol of the formula:

where n is an integer, preferably the number 9 or 10. Nonoxynol-9 and nonoxynol-10 are preferred, especially when these compounds meet the USP 22 regulations.

The preparation according to the invention is very easy to apply. It can be inserted into the vagina, for example with a finger, cut to the desired size, for example 5x5 cm. A foreign body sensation is felt, if at all, only in the first minutes after insertion. Through the action of body heat and / or from the secretions present in the vagina, the active ingredient (s) contained in the film have a better and more uniform effect compared to other, especially solid, galenic forms. The pharmaceutical effect to be achieved depends on the combination of active ingredients used.

The following examples serve to illustrate the present invention.

example 1 Vaginal preparation against bacterial infections

A mixture of 4.53 kg of polyvinyl alcohol Poval 205 from Kuraray Co, Ltd., Japan, 360 g of glycerol, 2.16 kg of nonoxynol-9 and 600 g of benzalkonium chloride was slowly brought to a temperature of 90 in 17.35 kg of water with stirring C warmed. After all components had dissolved, the slightly cloudy solution was cooled and filtered at a temperature of 50 ° C. The clear filtrate was left at a temperature of 45 C for 30 minutes, after which there were no air bubbles in the mixture. This film casting solution was used to produce a homogeneous film with a thickness of 0.09 millimeters on a film casting machine. The film casting solution was cast at a temperature of 40 ° C to 50 ° C.

Example 2 Vaginal preparation against trichomonads

A mixture of 453 mg of polyvinyl alcohol Poval 205 from Kuraray Co, Ltd., Japan, 36 mg of glycerol, 216 mg of nonoxynol-9 and 100 mg of metronidazole was dissolved in 10 ml of water and heated to 90 ° C. with stirring. The slightly cloudy solution was cooled and filtered at a temperature of 50 ° C. This filtrate was poured into a rectangular tub (5x10 cm) and dried with a heat lamp (Biccatherm lamp). A homogeneous film with a thickness of 0.075 millimeters was obtained.

Example 3 Vaginal preparation for the control of fungi

A mixture of 3.01 kg of polyvinyl alcohol Poval 205 from Kuraray Co, Ltd., Japan, 240 g of glycerol and 1.0 kg of nonoxynol was slowly heated to a temperature of 90 ° C. in 13.35 kg of water with stirring. The slightly cloudy solution was cooled and filtered at a temperature of 50 ° C. A slurry of 400 g of finely ground econazole in 2.0 kg of water at a temperature of 35 ° C. was added to this clear filtrate with stirring. This mixture was gently stirred at a temperature of 35 ° C. for 30 minutes, after which no air bubbles were present in the mixture. This film casting solution was used to produce a homogeneous film with a thickness of 0.07 millimeters on a film casting machine. The film casting solution was cast at a temperature of 35 ° C.

Claims (8)

Claims for the following contracting state: ES 1. Process for the preparation of a pharmaceutical preparation to be administered vaginally, characterized in that at least one water-soluble polyvinyl alcohol, at least one component A, selected from the group consisting of wetting agents, nonionic surface-active agents and dispersants , and at least one active ingredient B for the local treatment of sexually transmitted, resp. transmitted diseases, and / or vaginal infections, and optionally one or more excipient (s), mixed with water, and optionally at least one organic solvent, and homogeneously distributed with heating, for example to a temperature of about 90 ° C., the mixture obtained is poured and the existing solvents removed. 2. The method according to claim 1, characterized in that the active ingredient B is an active ingredient for the local treatment of bacterial or viral infections, for example benzalkonium chloride, a neomycin, such as neomycin B sulfate, or a polymyxin, such as polymyxin B sulfate , or an active ingredient for the local treatment of diseases caused by fungi or trichomonads, for example econazole, econazole nitrate, metronidazole, or an active ingredient for the treatment of vaginal mucosal affections, for example a placenta extract, these active ingredients optionally being mixed with at least one nonoxynol, such as nonoxynols formula

where n is an integer, preferably the number 9 or 10. 3. The method according to any one of claims 1 to 2, characterized in that the component A is selected from monohydric alcohols, for example a nonoxynol, such as nonoxynol-9, nonoxynol-10, and polyhydric alcohols, for example propylene glycol, glycerol, and in particular a Mixture of a nonoxynol and glycerin. 4. The method according to any one of claims 1 to 3, characterized in that the mixing ratio is adjusted so that the preparation 50 to 70 wt .-%, in particular 55 to 65 wt .-%, polyvinyl alcohol, 15 to 35 wt .-% , in particular 20 to 30% by weight, nonoxynol, 3 to 8% by weight, in particular 5% by weight, glycerol, and up to 15% by weight of active compound B, the sum of all constituents, including, if appropriate existing auxiliaries, each 100% by weight. 5. The method according to any one of claims 1 to 4, characterized in that the auxiliaries are selected from stabilizers, plasticizers, buffers, antioxidants, perfume and dyes, and that the auxiliaries are each present in effective concentrations. 6. The method according to any one of claims 1 to 5, characterized in that the mixture is filtered before pouring. 7. The method according to any one of claims 1 to 6, characterized in that the preparation in the form of a film with a layer thickness of 0.05 to 0.5 mm, in particular 0.06 to 0.2 mm, preferably 0.07 to 0.15 mm. 8. The method according to any one of claims 1 to 7, characterized in that the surface of the film is enlarged by embossing.